Significant challenges of tumor cells recognition, in-depth light penetration and in situ monitoring are confronted by scientists to develop photodynamic therapy (PDT) as reliable clinical treatment for cancers. To address the penetration depth and molecular imaging issues, the utilization of near-infrared (NIR) excitation (via multi-photon/up-conversion processes) and emission within the “biological windows” (such as 1st window: 600-950 nm, 2nd window: 1-1.35 μm and 3rd window: 1.5-1.8 μm) has provided a satisfying resolution since NIR photons can penetrate deep into the tissue and re-emit sharply without being absorbed by the cell even in the blood media and causing damage. Clear images can be obtained and differentiated then from the usual biological auto-fluorescence background. Recently, two-photon absorption photodynamic therapy (TPA-PDT) has received increasing attention. Porphyrin-based photosensitizers are considered as the prime candidates as their two-photon (TP) induced singlet oxygen (1O2) generation and red/near-infrared emission (˜650 nm & ˜750 nm) are very efficient and intense. Several design strategies for TPA-PDT photosensitizers have been reported in the literature, but only very few of those compounds are tumor cell-specific or have been investigated in vitro and in vivo, concerning especially porphyrins and lanthanides. For instance, selective closure of blood vessels through two-photon excitation PDT in vivo using porphyrin dimers of large TP absorption cross section has been demonstrated currently; tumor selectivity of amphiphilic photosensitizers has also been found related to their efficient binding to low-density lipoproteins which are responsible for the transport of porphyrins to tumor tissues. High molecular-weight porphyrins, in essence, preferentially accumulate on solid tumors and are expected to be internalized into membrane-limited organelles, thereby achieving controlled localization in the intercellular compartment. However, it has still been arduous for PDT probes to come into contact with cancer cells in particular, with two major problems being associated with commercially available or literature-reporting photosensitizers for photodynamic treatment: (i) the recognition of cancer cells and (ii) the monitoring of their effectiveness. In this regard, the Applicants of the present invention had reported previously in Zhang T, Chan C F, Hao J H, Law G L, Wong W K and Wong K L (2013). Fast Uptake, water-soluble, mitochondria-specific erbium complex for dual function molecular probe—imaging and photodynamic therapy. RSC Adv 3, 382-385, a specific phospholipid marker—an ytterbium-porphyrin complex (Yb—N) which has a strong binding with anionic phospholipid species in solution and can identify several of them in a number of cancer cells via long-lived visible-to-NIR lanthanide luminescence. A limitation of this complex is that it does not photo-generate 1O2. Without the advances in stem cell and gene therapy against cancers for 100% efficiency, it is always essential to explore any potential alternative methodology for the sake of human well-being.
It is an objective of the present invention to provide for PDT probes that solve the following three problems, namely (i) the recognition of cancer cells; (ii) the monitoring of their effectiveness and (iii) photo-generating 1O2—singlet oxygen.